Partial breast irradiation (PBI) has recently received alot of attention, especially since the FDA approval of a balloon-type brachytherapy applicator. This therapeutic approach is intended for highly selected patients with early invasive carcinoma of the breast with low-risk for local failure. There is limited data comparing the effectiveness of PBI to conventional BCT. This study tests the safety of PBI with interstitial HDR brachytherapy (HDR-BT) after breast conserving surgery (BCS) for T1 breast cancer in a phase I-II study, and to present the initial findings of a phase III trial comparing the efficacy of tumor bed irradiation (TBRT) alone with conventional whole breast radiotherapy (WBRT).

HDR-BT consisting of seven fractions of 4.33 Gy (n = 8) or seven fractions of × 5.2 Gy given two per day (n = 37) was delivered to the tumor bed.

Based on the results of this phase I-II study, 222 additional patients were randomized to receive WBRT (50 Gy in fractions of 2 Gy) or TBRT alone.

Approximately 2/3 of the TBRT group consisted of patients treated with seven fractions of 5.2 Gy HDR-BT and 1/3 of patients treated with 50 Gy wide field electron irradiation in patients unsuitable for brachytherapy.

The eligibility criteria for both studies were: unifocal T1 disease, uninvolved margins of resection, no more than microscopic axillary node involvement, no grade 3 tumors, no in-situ carcinomas, no lobular carcinomas, and no EIC.

The two arms were well balanced.

Breast cancer related events and side effects were assessed. For late side effects only patients with a minimum follow-up of 20 months were evaluated.

Both local failures were salvaged with breast conserving surgery and whole breast radiotherapy.

The 6-year probability of cancer-specific (CSS), relapse-free (RFS) and local recurrence-free survival (LRFS) was 90.0%, 85.9% and 95.6%, respectively.

The cosmetic results were judged to be excellent in 44 out of 45 patients (97.8%). Severe (> G 2) skin sequalae or fibrosis was not found. Symptomatic fat necrosis occured in 2 (4.4%) patients.

Phase III study: At a median follow-up of 28 months, 1 patient in each arm has developed local recurrence, both of which were in the tumor bed. Both local failures were salvaged with breast conserving surgery and whole breast radiotherapy.

The 3-year probability of CSS, RFS and LRFS was 98%, 96% and 98% in the WBRT group and 100%, 94% and 98% in the TBRT group, respectively (p = NS).

There was no significant difference between the two treatment arms regarding the incidence of radiation side effects. There was one case of grade 3 fibrosis in the brachytherapy group. TBRT was significantly more cost effective than WBRT.

There was evidence of a learning curve for the brachytherapy procedure including the placement of more catheters per implant, bigger volume coverege by therapeutic doses, and better dose homogeneity as a function of time.

Author's Conclusions

Five-year results of our phase I-II study prove that sole HDR-BT of the tumor bed with careful patient selection and adequate quality assurance is a feasible alternative to WBRT.

At a median follow-up of 30 months in phase III study, HDR-BT alone is similar to WBRT with respect to skin and parenchymal side effects.

Clinical/Scientific Implications

Longer follow-up is required to draw a final conclusion regarding the difference in local control rate between the two treatment arms. Promising early results support further accrual into ongoing trials of this and similar approaches. There is a learning curve associate with this techniques probably requiring special training. This could be a reasonable approach for highly selected patients with limited access to conventional BCT practices.

Oncolink's ASTRO Coverage made possible by an unrestricted Educational Grant from Ortho Biotech.